This R03 grant application, submitted in response to RFA-DA-05-004 "Lapse and Relapse to Drug Abuse and Other Chronic Conditions," proposes an interdisciplinary project with collaborations between clinical and basic scientists to examine the roles of cue-reactivity and genetic polymorphisms as possible etiological mechanisms in the relapse to cocaine use. This represents one of the few studies of relapse in human populations to combine laboratory-based measures with community-based follow-up to understand the biological and behavioral foundations of relapse to cocaine. The specific aims of the study are to: (1) examine whether drug-free cocaine dependent cue-reactive individuals are more likely to relapse than nonreactive individuals; (2) determine whether cue-elicited craving responses are significantly different in cocaine dependent individuals with polymorphisms in candidate genes in the dopamine and beta-endorphin pathways compared to individuals without the polymorphisms; and (3) determine whether individuals with genetic polymorphisms are more likely to relapse with cocaine than those without the genetic polymorphisms. This proposed project will be an "add-on" to an existing five-year Center for Substance Abuse Treatment grant (CSAT) awarded to Drs. Smelson and Kline and funded through 2009. The CSAT grant targets 550 individuals with a substance abuse disorder entering treatment at the Department of Veterans Affairs New Jersey Health Care System (VANJ). This proposed R03 will recruit a subgroup of 105 African American males with a confirmed diagnosis of cocaine dependence who are enrolled in the CSAT project. Those recruited into this R03 study will undergo a baseline assessment battery, cue-exposure procedure, blood withdrawal for genetic analysis, and urine toxicology screening. The subjects will be reassessed with the Addiction Severity Index and urine toxicology screen at six months post-baseline through the CSAT project to determine relapse to cocaine. This project represents a broad exploratory transdisciplinary effort to better understand the clinical, behavioral and biological bases of relapse and will serve as the foundation for a future R01 submission. This study will help further our understanding of the mechanisms underlying relapse to cocaine and lead to the development of more effective relapse prevention strategies and pharmacogenetic treatments.